Activation of aflatoxin B1 by primary cultures of adult rat hepatocytes: effects of hepatocyte density.
Primary monolayer cultures of adult rat hepatocytes readily activate aflatoxin B1 as determined by bacterial mutagenesis (Ames test) and the extent of apparent covalent binding of aflatoxin B1 residues to hepatocyte macromolecules. For intact cultures inoculated with 3 X 10(5)-3 X 10(6) cells/dish, the efficiency of activation decreases with increasing cell density whereas permeabilized hepatocytes prepared from similarly-handled monolayer cultures show with increasing protein proportional increases in the capacity to activate aflatoxin B1. The density effect observed with intact cultured hepatocytes appears not to be due to substrate (aflatoxin B1) or oxygen depletion. These findings have apparent relevance to studies of carcinogen metabolism and in the design of carcinogen/mutagen testing protocols which utilize cultured hepatocytes.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009153:Mutagens; D051381:Rats
D000348:Aflatoxins; D009153:Mutagens; D016604:Aflatoxin B1